Allergic diseases are of great public health concern as more than 20% of the U.S. population alone are afflicted with these chronic and often debilitating diseases. In particular, despite increased usage of medications, deaths from asthma have risen by 72%. These findings highlight the need for improved therapeutic strategies.
Allergic diseases (including allergic rhinitis, allergic dermatitis, and allergic asthma) are characterized by tissue inflammatory responses. Numerous clinical and experimental animal studies have indicated a pivotal role of cytokines in the development of allergic inflammatory responses. In particular, a subset (Th2) of CD4.sup.+ T cells, which has been distinguished functionally by its pattern of cytokine secretion, is thought to play a key role. Th2 cells are thought to promote allergic responses through their secretion of the cytokines, IL-4 and IL-5, which promote IgE production and mast cell development, and eosinophilia, respectively. Cytokines released by the opposing pathway (Th1), such as IFN-.gamma., inhibit the development and expansion of Th2 cells and cytokine production.
Airway hyperreactivity seen in asthma is associated with an inflammatory response characterized by the presence of eosinophils and activated T.sub.H2 -lymphocytes infiltrating the bronchial mucosa (8, 9, 10, 11, 13, 15, 16). However, the sequence of events leading to inflammatory responses and bronchial hyperreactivity are still unclear. The precise regulatory role of T cells and cytokines involved in the inflammatory responses are as yet to be determined.
It has been previously suggested that IFN-.gamma. may prove beneficial in the treatment of allergic responses in mice (9, 16, 20). In a pilot study to evaluate the effects of nebulized recombinant IFN-.gamma. protein in patients with mild atopic asthma, Boguniewicz et al. (2) demonstrated that four of five patients had a decrease in the percent of eosinophils, however, no improvement in pulmonary function was observed in any patient. In addition, they showed that there was no significant decrease in airway inflammation associated with nebulized IFN-.gamma.. Previous studies in murine models of allergy have demonstrated that short term systemic delivery of IFN-.gamma. did not provide sufficiently high levels of IFN-.gamma. in the lungs, and consequently was not effective in reversing antigen-induced allergic responses (16). In addition, recombinant IFN-.gamma. given systemically has severe side effects, such as fever, impaired function of the kidneys, and heart, leucocytopenia, and considerable loss of weight. However, short term nebulization of IFN-.gamma. to normal human airways did not induce such effects. Injected cytokine proteins are often short-lived and dissipate quickly in vivo, which limits their potential in vivo therapeutic use. Moreover, repeated injections are required to reach therapeutic efficacy. Thus there is a need in the art for new methods for delivering cytokines to the critical portions of the body for treatment of antigen-induced allergies.